Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-dependent diabetes mellitus (IDDM) susceptibility determinants are known to be associated with both HLA-DR3 and -DR4. We monitored the inheritance of HLA-DR alleles in 37 families in which IDDM affected one parent and at least one offspring in order to try to learn more about the modes of inheritance of IDDM determinants. Ninety-seven insulin-dependent diabetics whose parents did not have diabetes and 158 nondiabetics were used as control groups for estimates of DR allele frequencies in the overall diabetic and general populations. The proportion of diabetic parents who transmitted DR4 to diabetic offspring (78%) was significantly higher (P less than 0.001) than the gene frequency of DR4 in the overall diabetic population (43%). The proportion of nondiabetic parents who transmitted DR4 to diabetic offspring (22%) was not significantly different from the gene frequency of DR4 in the nondiabetic population (16%), but it was significantly lower (P less than 0.05) than the gene frequency in the overall IDDM population. These proportions suggest that inheritance of the DR4-associated IDDM susceptibility determinant is not recessive, because in recessive inheritance expression of a trait depends on each parent contributing a susceptibility determinant. The proportions of diabetic and nondiabetic parents who transmitted the DR allele associated with the susceptibility determinant would then equal one another. The transmission of predominantly DR4 from affected parents to affected offspring suggests that susceptibility to IDDM is inherited primarily via a single dose of a potent determinant associated with DR4, as in dominant inheritance. When DR3 was transmitted at all it was usually by the nondiabetic parent. Only 8% of diabetic parents transmitted DR3 but 35% of nondiabetic parents transmitted DR3. The proportion of nondiabetic parents who transmitted DR3 was similar to the gene frequency of DR3 in the overall diabetic population (29%), but it was significantly higher than the gene frequency of DR3 in the nondiabetic population (15%; P less than 0.005). The percentage of diabetic offspring with the genotype DR3DR4 (35%) was identical to the percentage of individuals in the overall IDDM population with this genotype (35%). Numerous population data indicate that the DR3DR4 genotype carries a higher relative risk for IDDM than any other genotype, which suggests synergism between the DR3- and DR4-associated determinants. The family data reported here support this synergism but suggest that the DR4-associated determinant can give substantial susceptibility independent of the DR3-associated determinant and that the DR3-associated determinant is often expressed as enhancing susceptibility in the presence of the dominant DR4- associated determinant.
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PMID:HLA-DR4 in insulin-dependent diabetic parents and their diabetic offspring: a clue to dominant inheritance. 348 37

Type 1 diabetes is said to be extremely rare in children in India, where diabetes treated with insulin may be due to chronic pancreatic disease or malnutrition. To see whether typical type 1 diabetes occurred in Asian children in the United Kingdom, all known Asian children with diabetes in industrial West Yorkshire were ascertained. A total of 17 such children were studied; of these, seven were from three multiplex families and two fathers from these families had diabetes. All children were ketosis prone and developed diabetes while resident in the UK. There were significant increases in HLA-B8 and HLA-DR3 and increases in HLA-DR4 and HLA-DR3/DR4, while HLA-B15 was absent. Islet cell antibodies, either IgG or complement fixing, were present in four of 18 subjects tested, all of whom had disease of short duration. The prevalence of type 1 diabetes in Asian children aged 15 years or less in West Yorkshire was 36/100,000, assuming complete ascertainment. It is concluded that typical type 1 diabetes may occur in Asian children and this condition may be more common in families who have migrated to the UK.
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PMID:Insulin dependent diabetes in Asians. 349 31

We have studied HLA-A, -B, -C, -DR, and -DQ antigen frequencies in 63 Type 1 diabetic Arab patients resident in Kuwait. Both HLA-DR3 (relative risk (RR) = 5.80) and -DR4 (RR = 2.87) showed positive associations with Type I diabetes mellitus in these patients whilst -DR2 (RR 0.16) and -DR5 (RR = 0.15) were negatively associated. The strong positive association with both HLA-DR3 and -DR4 was confirmed in Non-Gulf Arabs (RR = 12.55 and 4.29, respectively) whereas the Gulf Arabs had a significant positive association with HLA-DR3 (RR = 4.41) only. The disease was negatively associated with HLA-DR2 (RR = 0.05) in Gulf Arab patients only and with HLA-DR5 (RR = 0.10) in Non-Gulf Arabs only. HLA-DRw52 and -DRw53 were increased in Non-Gulf Arabs only (RR = 3.14 and 4.63, respectively). In both groups there was strong association with HLA-DQ3 (Gulf, RR = 28.11; Non-Gulf, RR = 6.25). Amongst HLA-A, -B, and -C loci, there was a positive association with HLA-B8 (RR = 19.06).
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PMID:HLA associations in an Arab type 1 diabetic population. 350 87

One hundred ninety-nine gravida with gestational diabetes mellitus (GDM) defined as "carbohydrate intolerance of varying severity with onset or first recognition during pregnancy" have been stratified into subgroups on the basis of fasting plasma glucose and evaluated for further phenotypic and genotypic heterogeneity. A significantly greater proportion of the women in all our groups were older and heavier than in a "control" population of 148 consecutive gravida with documented normal oral glucose tolerance. After correction for age and weight by covariate analysis, absolute insulinopenia in response to oral glucose could be demonstrated in all GDM groups, although exceptions were present in each. The incidence of diabetes in the mothers of our patients with GDM was 8-fold greater than in controls; the incidence in fathers did not deviate from control patterns. HLA-DR3 and DR4 antigens were more frequently present in GDM and the increase was statistically significant in blacks. At the time of diagnosis, cytoplasmic islet cell antibodies (ICA) were significantly more common in GDM associated with elevated fasting plasma glucose than in controls; the frequency of ICA was 18.4% (7/38) in women with fasting plasma glucose greater than or equal to 130 mg/dl. Our findings indicate that GDM entails genotypic as well as phenotypic diversity and may include patients with slowly-evolving Type I diabetes mellitus, as well as patients with Type II diabetes mellitus, and women with asymptomatic diabetes which antedated the pregnancy (i.e. pregestational diabetes mellitus). Appreciation of this heterogeneity should be incorporated into any evaluation of intervention strategies for women with GDM or into prognoses concerning their postpartum metabolic status.
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PMID:Gestational diabetes mellitus: a syndrome with phenotypic and genotypic heterogeneity. 352 23

The relative risks (RR) of the immunogenetic markers of insulin-dependent diabetes mellitus (IDDM) have been calculated in a population of 235 IDDM patients compared with a control population. The highest relative risk was that of subjects heterozygous DR3/DR4 (RR = 47, P less than 0.001) which was still more increased in those who carry this combination associated with the RFLP cluster DQR4 (RR = 72). Further, a sample of 51 secondary affected siblings of IDD index cases has been compared with 265 non affected siblings (one child of each family, excluding index cases). The highest risks have been found in addition to DR3/DR4, for DR3 alone and particularly for the combination C4BQ0, DR3 (RR = 9, p less than 0.001) suggesting a role for this peculiar association in the familial penetrance. In the group of siblings HLA-identical with the index case, only two factors showed some capacity of discriminating between affected and non affected siblings: HLA-DR3 and age (less than or equal to 10 years old at onset of IDDM in the index case) (p less than 0.01). In the group of haploidentical siblings, the combination DR3/DR4 and the associations C4BQ0, DR3 and BfF1, DR3 significantly increased the susceptibility for higher familial occurrence of the disease. If confirmed by additional family series, this scale of risk factors could be helpful in predicting risk of IDDM to siblings of diabetic children.
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PMID:[Risk factors in insulin-dependent diabetes]. 353 93

The frequency distribution of alleles controlled by the factor B (Bf) and glyoxalase genes that are found close to the HLA system on chromosome 6 was studied in 170 insulin-dependent diabetic patients. The data were compared with those for HLA-A, -B and -DR antigens and were related to age of onset of diabetes. All the diabetics were ketosis prone and on permanent insulin therapy. A significant excess of BfF1 was seen in the diabetic patients (p less than 10(-4]. Glyoxalase frequency distribution showed no significant deviation from controls, whereas HLA-DR3 (p less than 10(-4] HLA-DR4 (p less than 10(-4] were increased. Breakdown of data by age of diagnosis of disease showed no increase in the frequency of BfF1 and GLO1-2 but an increase of HLA DR3 and DR4 in patients with early onset diabetes. The findings of the study are consistent with data reported by others investigators and support the notion that one or more genes mapping close to the HLA A. B and DR and to the Bf loci confer susceptibility to insulin dependent diabetes.
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PMID:Factor B (Bf) and glyoxalase genes in insulin-dependent diabetes mellitus. 385 41

It is now well established that HLA system is involved in the susceptibility to Type 1 diabetes mellitus. In this study we look for a possible effect of the Gm system. A first study (cases-controls) suggests that among individuals who had HLA-DR3 but not HLA-DR4 or HLA-DR4 without HLA-DR3, there is a possible effect of the phenotype Gm3,23,5 or Gm3,-5 in the susceptibility to IDDM. Moreover, we have tested by the sibpair method whether HLA and Gm are transmitted independently from IDDM: an unaffected sib, sharing the same HLA haplotypes than an affected individual, seems to be more often phenotypically different at the Gm loci.
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PMID:[Interaction between HLA and Gm for susceptibility to insulin-dependent diabetes]. 386 88

In a prospective screening program for type I diabetes mellitus, we identified a unique family in which several members (mother and three siblings) expressed an unusual set of HLA-DR alleles (DR2+, DR3/4-) and were in different phases of immunologically mediated islet beta cell dysfunction. Immunologic and/or clinical manifestations of type I diabetes were absent in all siblings not sharing both HLA haplotypes in common with the proband. This article illustrates: the clinical utility of prospective family screening for predictive markers, such as islet cell antibodies, progressive autoimmune beta cell destruction can occur in the absence of the "high-risk" alleles HLA-DR3 and DR4, and HLA identity with the proband, rather than specific HLA alleles, i.e., presence of DR3, DR4 and absence of DR2, is an essential factor.
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PMID:Progressive autoimmune beta cell insufficiency: occurrence in the absence of high-risk HLA alleles DR3, DR4. 387 22

Immunoglobulin heavy and light chain genes are often discussed as susceptibility genes for insulin dependent (type 1) diabetes mellitus (IDDM) in addition to HLA-DR3 and DR4. Accordingly we analysed 175 unrelated patients for an interaction between immunoglobulin allotype antigens (Gm) and HLA. While DR3 and DR4 antigens and DR3/DR4 heterozygotes occur significantly more often among diabetics than among normal controls, their Gm allotype frequencies are very similar. An interaction between special Gm allotypes and phenotypes, on the one side, and DR3, DR4 or DR3, 4 on the other side could not be demonstrated.
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PMID:No interaction between HLA and immunoglobulin IgG heavy chain allotypes in early onset type 1 diabetes. 393 24

The families of 41 probands with type I (insulin-dependent) diabetes mellitus (IDDM) were typed for HLA-A, HLA-B, and HLA-DR antigens in addition to the complement polymorphisms C2, C4A, C4B, and Bf. All of these loci are encoded on the short arm of human chromosome 6 in a narrow region. Alleles at HLA-B (8, 15, 18, and 40), HLA-DR (3 and 4), and Bf (F1) have been associated with increased relative risk (RR) for IDDM, while HLA-B7 and HLA-DR2 have been associated with decreased RR for IDDM. This study confirms those significant risks in addition to confirming increased risk for the null (silent) allele for C4A (C4AQ0) and a rare C4B variant (C4B2.9). The significantly associated antigens (alleles) and risks were: HLA-B8 (RR = 3.1), HLA-DR3 (RR = 5.2), HLA-DR4 (RR = 4.3), and BfF1 (RR = 7.1), in addition to C4AQ0 (RR = 2.8) and C4B2.9 (RR = 12.6). Significantly low risk was associated only with HLA-DR2 (RR = 0.1). In a recent study, we defined five high-risk haplotypes that were determined solely by HLA-B, Bf, and HLA-DR (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4). By inclusion of information from the complement polymorphism, we have defined in greater detail three of these five high-risk haplotypes. One previously identified haplotype (B40-BfS-DR4) showed no complement clustering, while the rare high-risk haplotype (B8-BfS-DR4) was seen only once in this smaller sample.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Complement and HLA. Further definition of high-risk haplotypes in insulin-dependent diabetes. 398 76


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